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Validation of an online tool for early prediction of the failure-risk in gestational trophoblastic neoplasia patients treated with methotrexate

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Abstract

Purpose

In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics.org/hCG. The objective was to confirm the validity of the website estimations with respect to NM.

Methods

The consistencies of modeled hCGres estimated by NM and by the website were assessed in a dataset of 60 fictive patients with simulated hCG profiles, as well as in an independent database of 531 actual patients. Moreover, the hCGres predictive values regarding MTX failure-risk were assessed.

Results

The values of hCGres obtained with both methods were highly consistent in the fictive patient and in the actual patient datasets: median relative prediction errors (RPE) were − 0.059 and 9.9 × 10–7, respectively. The ROC AUCs for predictions of MTX failure-risk were 0.90 (95% CI 0.87,0.93) with both NM and the website. The gradual association between increasing hCGres and the 2-year MTX failure-free survival was confirmed.

Conclusion

There is a high consistency of hCGres estimates obtained with the two methods. The website is meant to help clinicians in the interpretation of hCG decline curves of MTX-treated GTN patients. hCGres is now validated for more than 1690 patients in four independent datasets, and its recognition as an early predictor of MTX resistance for treatment adjustment and for the future studies should be considered.

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Abbreviations

AUC:

Area-under-the-curve

EMA:

European medicines agency

FDA:

Food and drug administration

FIGO:

Federation of gynecology and obstetrics

GTN:

Gestational trophoblastic neoplasia

hCG:

Human chorionic gonadotropin

hCGres:

HCG residual concentration

MTX:

Methotrexate

NM:

NONMEM program®

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Authors and Affiliations

  1. Oncology Medical Department, CITOHL, Université Claude Bernard Lyon-1, Hospices Civils de Lyon, Lyon, France

    Kathleen Dekeister, Gilles Freyer & Benoit You

  2. EMR 3738 Ciblage Thérapeutique en Oncologie, Faculté de Médecine Lyon-Sud, BP12, 69310, Pierre-Bénite Cedex, France

    Kathleen Dekeister, Michel Tod, Rémi Tod, Olivier Colomban, Gilles Freyer, François Golfier & Benoit You

  3. French Trophoblastic Disease Reference, Hospices Civils de Lyon, Lyon, France

    Pierre-Adrien Bolze, Jérôme Massardier, Touria Hajri, François Golfier & Benoit You

  4. Gynecology-Obstetrics Department, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France

    Pierre-Adrien Bolze & François Golfier

  5. Gynecology-Obstetrics Department, Centre Hospitalier Femme Mère Enfant, Bron, France

    Jérôme Massardier

  6. Oncology Medical Department, Groupe Hospitalier APHP, Sorbonne Université, Hôpital Tenon, Paris, France

    Jean-Pierre Lotz

  7. Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College London, London, W68RF, UK

    Michael J. Seckl

  8. Gynecology-Obstetrics Department, Sunnybrook Health Sciences Centre, Toronto, Canada

    Ray Osborne

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  1. Kathleen Dekeister
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  2. Pierre-Adrien Bolze
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Correspondence to Kathleen Dekeister.

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Dekeister, K., Bolze, PA., Tod, M. et al. Validation of an online tool for early prediction of the failure-risk in gestational trophoblastic neoplasia patients treated with methotrexate. Cancer Chemother Pharmacol 86, 15–24 (2020). https://doi.org/10.1007/s00280-020-04086-0

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